Signal transduction is central to the understanding of cancer cell growth, metastasis and the molecular basis of cancer response to therapy. With the advent of proteomics, future cancer treatment strategies could be tailored to target specific signaling pathways for an individual, based on an individual tumor?s genetic background. Thus, it is possible that new adjuvant therapies can be developed and used with existing treatment regimens to target differential expression of signaling proteins in patients predicted to be non- or poor responders. Our overall research goal is to identify molecular changes in cell signaling proteins that occur in cancer and target these proteins or genetic changes for the development of new therapies. Project #1: will address the role of PI 3-kinase mediated signaling in angiogenesis and the identification of novel downstream signaling proteins as targets for anti-angiogenic therapy. Project #2: will address the signal transduction pathways that govern neutrophil activation and how these signals might differ in cancer patients who have undergone blood and marrow transplantation. Project #3: will examine how cellular signals induce expression and activation of DNA repair enzymes in ovarian cancer with a special emphasis on angiogenesis. Project #4: will address the role of cytochrome P450-1A1 and -1A2 isoforms in carcinogenesis and will use molecular modeling techniques to design novel inhibitors that could prevent metabolism of environmental pollutants into carcinogens. Project #5: proposes to design new microfluidic methods for proteomic analysis that will rapidly evaluate protein expression from small sample sizes for identification. Each of these molecular changes will be analyzed as indicators for prognosis, diagnosis, treatment and outcome and may reveal a strategy for treating patients who respond poorly to conventional therapies. These projects will be led by junior faculty, who will be mentored by an administrative core. To support these research efforts, two core facilities are also proposed for fluorescence activated cell sorter/cell separator (FACS) and mass spectrometry. In addition, faculty recruitment in the area of signal transduction and cancer are also proposed, which will expand the critical mass of cancer research scientist who study signal transduction in cancer and encourage greater collaborative efforts. Our long term goal is to create a strong basic science core that will support cancer research/education and clinical treatment for the citizens of WV and the surrounding Appalachia region.